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e s e a r c h.. f o c u s :
Studies
of the functions, traffic, and inhibition of fungal adhesins
The
ability of fungal cells to colonize different substrates and persist
in diverse environments frequently involves regulated changes in
their ability to bind substrates and/or one another; such changes
are mediated cell surface adhesion proteins known as adhesins. We
are dissecting the functions of model adhesins in the simple and
easily manipulated system of budding yeast. In a complementary approach,
we are applying methodologies for the directed identification of
lead compounds with high specificity to functional domains of budding
yeast adhesion proteins and major determinants of adhesion in the
human pathogenic yeast Candida albicans. Such compounds are a means
of developing novel antifungal drugs that disrupt fungal adhesion
interactions. Drugs of this kind may have both stand-alone prophylactic
value and combinatorial synergy with other antifungal drugs presently
employed in immune-compromised patients suffering from systemic
fungal infections.
More
about fungal adhesins...
The genes encoding adhesion proteins often undergo dramatic regulation
in response to different life cycle transitions and in different
fungal species. Two species of interest to us, and in which a
large number of bona fide and candidate adhesion proteins are
already known, are budding yeast, S. cerevisiae and the human
commensal pathogen, Candida albicans. To be successful, pathogenic
cells must initially adhere tightly to host tissues (a heterotypic
adhesion interaction) and also, to a lesser extent, one another
(a homotypic adhesion interaction). The adhesion proteins identified
to date in these two fungal systems share a number of common domains
of protein sequence similarity and undergo common types of post-translational
modifications during their biogenesis that can be important to
their to their function and localization at the fungal cell surface.
Presently, the significance of these modifications and domains,
as well as the specific function of a number of the proteins that
contain them remain to be understood. Similarly, the cellular
processes that regulate the disposition of these proteins in the
fungal cell wall and that presumably therefore may represent virulence
factors, are also incompletely understood. Our aim is to learn
more about this important class of fungal proteins through a variety
of functional studies, including developing methods for rapidly
generating inhibitors of specific fungal adhesion proteins.
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more details about my other research, please select from the following:
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